nanoparticles

Stem Cell Roundup: Protein shows promise in treating deadliest form of breast cancer: mosquito spit primes our body for disease

/ Kevin McCormack / 1 Comment

Triple negative breast cancerTriple negative breast cancer is more aggressive and difficult to treat than other forms of the disease and, as a result, is more likely to spread throughout the body and to recur after treatment. Now a team at the University of Southern California have identified a protein that could help change that.

The research, published in the journal Nature Communications, showed that a protein called TAK1 allows cancer cells from the tumor to migrate to the lungs and then form new tumors which can spread throughout the body. There is already an FDA-approved drug called OXO that has been shown to block TAK1, but this does not survive in the blood so it’s hard to deliver to the lungs.

The USC team found a way of using nanoparticles, essentially a tiny delivery system, to take OXO and carry it to the lungs to attack the cancer cells and stop them spreading.

triple_negative_breast_cancer_particle_graphic-768x651In a news release Min Yu, the principal investigator on the team, said that although this has only been tested in mice the results are encouraging:

“For patients with triple-negative breast cancer, systemic chemotherapies are largely ineffective and highly toxic. So, nanoparticles are a promising approach for delivering more targeted treatments, such as OXO, to stop the deadly process of metastasis.”

Mosquito spit and your immune system

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Mosquito bite: Photo courtesy National Academy of Sciences

Anyone who has ever been bitten by a mosquito knows that it can be itchy and irritable for hours afterwards. But now scientists say the impact of that bite can last for much longer, days in fact, and even help prime your body for disease.

The scientists say that every time a mosquito bites you they inject saliva into the bite to keep the blood flowing freely. But that saliva also has an impact on your immune system, leaving it more vulnerable to diseases like malaria.

OK, so that’s fascinating, and really quite disgusting, but what does it have to do with stem cells? Well, researchers at the National Institute of Health’s (NIH) Malaria and Vector Research Laboratory in Phnom Penh, Cambodia engrafted human stem cells into mice to study the problem.

They found that mice with the human stem cells developed more severe symptoms of dengue fever if they were bitten by a mosquito than if they were just injected with dengue fever.

In an article in Popular Science Jessica Manning, an infectious disease expert at the NIH, said previously we had no idea that mosquito spit had such a big impact on us:

“The virus present in that mosquito’s saliva, it’s like a Trojan horse. Your body is distracted by the saliva [and] having an allergic reaction when really it should be having an antiviral reaction and fighting against the virus. Your body is unwittingly helping the virus establish infection because your immune system is sending in new waves of cells that this virus is able to infect.”

The good news is that if we can develop a vaccine against the saliva we may be able to protect people against malaria, dengue fever, Zika and other mosquito-borne diseases.

Stories that caught our eye: color me stem cells, delivering cell therapy with nanomagnets, and stem cell decisions

/ Todd Dubnicoff / Leave a comment

Nanomagnets: the future of targeted stem cell therapies? Your blood vessels are made up of tightly-packed endothelial cells. This barrier poses some big challenges for the delivery of drugs via the blood. While small molecules are able make their way through the small gaps in the blood vessel walls, larger drug molecules, including proteins and cells, are not able to penetrate the vessel to get therapies to diseased areas.

This week, researchers at Rice University report in Nature Communications on an ingenious technique using tiny magnets that may overcome this drug delivery problem.

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At left, the nanoparticles are evenly distributed among the microtubules that help give the cells their shape. At right, after a magnetic field is applied, the nanoparticles are pulled toward one end of the cells and change their shapes. Credit: Laboratory of Biomolecular Engineering and Nanomedicine/Rice University

Initial studies showed that adding magnetic nanoparticles to the endothelial cells and then applying a magnetic field affected the cells’ internal scaffolding, called microtubules. These structures are responsible for maintaining the tight cell to cell connections. The team took the studies a step further by growing the cells in specialized petri dishes containing tiny, tube-shaped channels. Applying a magnetic field to the cells caused the cell-cell junctions to form gaps, making the blood vessel structures leaky. Simply turning off the magnetic field closed up the gaps within a few hours.

Though a lot of research remains, the team aims to apply this on-demand induction of cell leakiness along with adding the magnetic nanoparticles to stem cell therapy products to help target the treatment to specific area. In a press release, team leader Dr. Gang Bao spoke about possible applications to arthritis therapy:

“The problem is how to accumulate therapeutic stem cells around the knee and keep them there. After injecting the nanoparticle-infused cells, we want to put an array of magnets around the knee to attract them.”

To differentiate or not differentiate: new insights During the body’s development, stem cells must differentiate, or specialize, into functional cells – like liver, heart, brain. But once that specialization occurs, the cells lose their pluripotency, or the ability to become any type of cell. So, stem cells must balance the need to differentiate with the need to make copies of itself to maintain an adequate supply of stem cells to complete the development process. And even after a fully formed baby is born, it’s still critical for adult stem cells to balance the need to regenerate damaged tissue versus stashing away a pool of stem cells in various organs for future regeneration and replacement of damaged or diseased tissues.

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Visualizing activation of Nanog gene activity (bright green spot) within cell nucleus. 
Image: Courtesy of Bony De Kumar, Ph.D., and Robb Krumlauf, Ph.D., Stowers Institute for Medical Research

A report this week in the Proceedings of the National Academy of Sciences finds evidence that the two separate processes – differentiation and pluripotency – directly communicate with each other as way to ensure a proper balance between the two states.

The study, carried out by researchers at Stowers Institute for Medical Research in Kansas City, Missouri, focused on the regulation of two genes: Nanog and Hox. Nanog is critical for maintaining a stem cell’s ability to become a specialized cell type. In fact, it’s one of the four genes initially used to reprogram adult cells back into induced pluripotent stem cells. The Hox gene family is responsible for generating a blueprint of the body plan in a developing embryo. Basically, the pattern of Hox gene activity helps generate the body plan, basically predetermining where the various body parts and organs will form.

Now, both Nanog and Hox proteins act by binding to DNA and turning on a cascade of other genes that ultimately maintain pluripotency or promote differentiation. By examining these other genes, the researchers were surprised to find that both Nanog and Hox were bound to both the pluripotency and differentiation genes. They also found that Nanog and Hox can directly inhibit each other. Taken together, these results suggest that exquisite control of both processes occurs cross regulation of gene activity.

Dr. Robb Krumlauf one of authors on the paper talked about the significance of the result in a press release:

“Over the past 10 to 20 years, biologists have shown that cells are actively assessing their environment, and that they have many fates they can choose. The regulatory loops we’ve found show how the dynamic nature of cells is being maintained.”

Color me stem cells Looking to improve your life and the life of those around you? Then we highly recommend you pay a visit to today’s issue of Right Turn, a regular Friday feature of  Signals, the official blog of CCRM, Canada’s public-private consortium supporting the development of regenerative medicine technologies.

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Collage sample of CCRM’s new coloring sheets. Image: copyright CCRM 2017

As part of an public outreach effort they have created four new coloring sheets that depict stem cells among other sciency topics. They’ve set up a DropBox link to download the pictures so you can get started right away.

Adult coloring has swept the nation as the hippest new pastime. And it’s not just a frivolous activity, as coloring has been shown to have many healthy benefits like reducing stressed and increasing creativity. Just watch any kid who colors. In fact, share these sheet with them, it’s intended for children too.

Stem cell stories that caught our eye: How Zika may impact adult brains; Move over CRISPR there’s a new kid in town; How our bodies store fat

/ Kevin McCormack / Leave a comment

Here are some stem cell stories that caught our eye this past week. Some are groundbreaking science, others are of personal interest to us, and still others are just fun.

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Zika mosquito

Zika virus could impact adult brains

It’s not just a baby’s developing brain that is vulnerable to the Zika virus, adult brains may be too. A new study shows that some stem cells that help repair damage in the adult brain can be impacted by Zika. This is the first time we’ve had any indication this could be a problem in a fully developed brain.

The study, in the journal Cell Stem Cell, looked at neural progenitors, a  stem cell that plays an important role in helping replace or repair damaged neurons, or nerve cells, in the brain. The researchers exposed the cells to the Zika virus and found that it infected the cells, causing some of the cells to die, and also limited the ability of the cells to proliferate.

In an interview in Healthday, Sujan Shresta, a researcher at the La Jolla Institute for Allergy and Immunology and one of the lead authors of the study, says although their work was done in adult mice, it may have implications for people:

“Zika can clearly enter the brains of adults and can wreak havoc. But it’s a complex disease, it’s catastrophic for early brain development, yet the majority of adults who are infected with Zika rarely show detectable symptoms. Its effect on the adult brain may be more subtle and now we know what to look for.”

Move over CRISPR, there’s a new gene-editing tool in town

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Jennifer Lopez: Photo courtesy MTV

For much of the last year the hottest topic in stem cell and gene editing research has been CRISPR and the ease with which it can be used to edit genes. It’s so hot that apparently it’s the title of an upcoming TV show starring Jeniffer Lopez.

But hold on J-Lo, a new study in Nature Communications says by the time the show is on the air it may be old hat. Researchers at Carnegie Mellon and Yale University have developed a new gene-editing system, one they claim is easier to use and more accurate than CRISPR. And to prove it, they say they have successfully cured a genetic blood disorder in mice, using a simple IV approach.

Tools like CRISPR use enzymes to cut open sections of DNA to edit a specific gene. It’s like using a pair of scissors to cut a piece of string that has a big knot in the middle; you cut out the knot then join the ends of the string together. The problem with CRISPR is that the enzymes it uses are quite large and hard to use in a living animal – let alone a human – so they have to remove the target cells from the body and do the editing in the lab. Another problem is that CRISPR sometimes cuts sections of DNA that the researchers don’t want cut and could lead to dangerous side effects.

Greater precision

The Carnegie Mellon/Yale team say their new method avoids both problems. They use nanoparticles that contain molecules made from peptide nucleic acid (PNA), a kind of artificial form of DNA. This PNA is engineered to be able to cut open DNA and bind to a specific target without cutting anything else.

The team used this approach to target the mutated gene in beta thalassemia, a blood disorder that can be fatal if left untreated. The therapy binds to the malfunctioning gene, enabling the body’s own DNA repair system to correct the problem.

In a news story in Science Daily Danith Ly, one of the lead authors on the study, says even though the technique was successful in editing the target genes just 7 percent of the time, that is way more than the 0.1 percent rate most other gene editing tools achieve.

“The effect may only be 7 percent, but that’s curative. In the case of this particular disease model, you don’t need a lot of correction. You don’t need 100 percent to see the phenotype return to normal.”

Hormone that controls if and when fat cells mature

Obesity is one of the fastest growing public health problems in the US and globally. Understanding the mechanisms behind how that happens could be key to finding ways to address it. Now researchers at Stanford University think they may have uncovered an important part of the answer.

Their findings, reported in Science Signaling, show that mature fat cells produce a hormone called Adamts1 which acts like a switch for surrounding stem cells, determining if they change into fat-storing cells.   People who eat a high-fat diet experience a change in their Adamst1 production, and that triggers the nearby stem cells to specialize and start storing fat.

There are still a lot of questions to be answered about Adamst1, including whether it acts alone or in conjunction with other as yet unknown hormones. But in an article in Health Canal, Brian Feldman, the senior author of the study, says they can now start looking at potential use of Adamst1 to fight obesity.

“That won’t be a simple answer. If you block fat formation, extra calories have to go somewhere in the body, and sending them somewhere else outside fat cells could be more detrimental to metabolism. We know from other researchers’ work that liver and muscle are both bad places to store fat, for example. We do think there are going to be opportunities for new treatments based on our discoveries, but not by simply blocking fat formation alone.”

 

Using baking ingredient to create “nano” bombs and destroy cancer stem cells

/ Kevin McCormack / Leave a comment

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“I am not a cook”. Richard Nixon and the baking ingredient that could help win the “war on cancer”

In 1971 President Richard Nixon declared a “war on cancer” and signed the National Cancer Act into law. Forty years later we’re still waging that war, and cancer is still one of the leading causes of death. But now researchers in Ohio have unveiled a new weapon; a nanobomb that targets cancer stem cells.

In treating invasive cancers the standard weapons are chemotherapy and radiation, but cancer stem cells are somehow able to evade these and lie dormant. Eventually they emerge from hiding and multiply and spread throughout the body, leading to a recurrence of the cancer.

So researchers at The Ohio State University Comprehensive Cancer Center turned to nanoparticles to try and target them. Nanoparticles for those of who aren’t up on the latest trendy science topics (something I plead guilty to) are particles between 1 and 100 nanometers in size. Just to put it in context, that’s about one billionth of a meter. In other words, very small indeed.

In the past when scientists tried to use nanoparticles to carry anti-cancer therapies such as therapeutic RNA to the tumor, the cancer cells simply enfolded the RNA nanoparticles in a kind of compartment called an endosome, which rendered them useless.

In a news release, principal investigator Xiaoming He said their new approach helps the nanoparticles escape from the endosomes and attack the cancer:

“We believe we’ve overcome this challenge by developing nanoparticles that include ammonium bicarbonate, a small molecule that vaporizes when exposing the nanoparticles to near-infrared laser light, causing the nanoparticle and endosome to burst, releasing the therapeutic RNA.”

In the study, published in Advanced Materials,   He and his team put micro-RNA miR-34a inside the nanoparticles. This is a molecule known to lower the levels of a  protein that cancer stem cells need for survival. When the ammonium bicarbonate was hit with the near-infrared laser it caused the endosomes to burst and released the miR-34a, killing the cancer cell.

When they tested this approach in a mouse model of human prostate cancer it significantly reduced the size of the tumors.

Because near-infrared lasers penetrate to about half an inch this method could be used for tumors near the skin surface, and for deeper ones would only require a minimally invasive surgery to deliver the necessary dose of light.

Ammonium bicarbonate, the ingredient used to help the nanoparticles swell up, is used by the food industry for some baked goods such as cookies and crackers. It’s a little odd to think that something used in such tasty treats could also be potentially deadly – think about that next time you are browsing the cookie aisle at the supermarket.

 

 

 

 

 

 

 

 

A Tumor’s Trojan Horse: CIRM Researchers Build Nanoparticles to Infiltrate Hard-to-Reach Tumors

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Some tumors are hard to find, while others are hard to destroy. Fortunately, a new research study from the University of California, Davis, has developed a new type of nanoparticle that could one day do both.

UC Davis scientists have developed a new type of nanoparticle to target tumor cells.

UC Davis scientists have developed a new type of nanoparticle to target tumor cells.

Reporting in the latest issue of Nature Communications, researchers in the laboratory of UC Davis’ Dr. Kit Lam describe a type of ‘dynamic nanoparticle’ that they created, which not only lights up tumors during an MRI or PET scan, but which may also serve as a microscopic transport vehicle, carrying chemotherapy drugs through the blood stream—and releasing them upon reaching the tumor.

This is not the first time scientists have attempted to develop nanoparticles for medicinal purposes, but is perhaps one of the more successful. As Yuanpei Li, one of the study’s co-first authors stated in a news release:

“These are amazingly useful particles. As a contrast agent, they make tumors easier to see on MRI and other scans. We can also use them as vehicles to deliver chemotherapy directly to tumors.”

Nanoparticles can be constructed out of virtually any material—but the material used often determines for what purpose they can be used. Nanoparticles made of gold-based materials, for example, may be strong for diagnostic purposes, but have been shown to have issues with safety and toxicity. On the flip side, nanoparticles made from biological materials are safer, but inherently lack imaging ability. What would be great, the team reasoned, was a new type of nanoparticle that had the best qualities of both.

In this study, which was funded in part by CIRM, Lam and the UC Davis team devised a new type of nanoparticle that was ‘just right,’—simple to make, safe and able to perform the desired task, in this case: attack tumors.

Built of organic porphyrin and cholic acid polymers and coated with the amino acid cysteine, the 32 nanometer-wide particles developed in this study offer a number of advantages over other models. They are small enough to pass into tumors, can be filled with a chemo agent and with a specially designed cysteine coating, and don’t accidentally release their payload before reaching their destination.

And this is where the truly ingenious part kicks in. With a simple flash of light, the researchers could direct the particles to drop their payload—at just the right time, offering some intriguing possibilities for new ways to deliver chemotherapy drugs.

But wait, there’s more. The fact that these new particles, which the team are calling cysteine nanoparticles, or CNP’s, appear to congregate inside tumors means that they also end up being easy to spot on an MRI.

Continued Li in the same release:

“These particles can combine imaging and therapeutics. We could potentially use them to simultaneously deliver treatment and monitor treatment efficacy. This is the first nanoparticle to perform so many different jobs. From delivering chemo, photodynamic and photothermal therapies to enhancing diagnostic imaging. It’s the complete package.”

And while the team cautions that these results are preliminary, they open the door to an entirely new and far more exact method of drug delivery to tumors—no matter how well-hidden in the body they may be.